No reliable gene expression biomarkers of current or impending neurocognitive impairment in peripheral blood monocytes of persons living with HIV

Events leading to and propagating neurocognitive impairment (NCI) in HIV-1-infected (HIV+) persons are largely mediated by peripheral blood monocytes. We previously identified expression levels of individual genes and gene networks in peripheral blood monocytes that correlated with neurocognitive functioning in HIV+ adults. Here, we expand upon those findings by examining if gene expression data at baseline is predictive of change in neurocognitive functioning 2 years later. We also attempt to validate the original findings in a new sample of HIV+ patients and determine if the findings are HIV specific by including HIV-uninfected (HIV?) participants as a comparison group. At two time points, messenger RNA (mRNA) was isolated from the monocytes of 123 HIV+ and 60 HIV? adults enrolled in the Multicenter AIDS Cohort Study and analyzed with the Illumina HT-12 v4 Expression BeadChip. All participants received baseline and follow-up neurocognitive testing 2 years after mRNA analysis. Data were analyzed using standard gene expression analysis and weighted gene co-expression network analysis with correction for multiple testing. Gene sets were analyzed for GO term enrichment. Only weak reproducibility of associations of single genes with neurocognitive functioning was observed, indicating that such measures are unreliable as biomarkers for HIV-related NCI; however, gene networks were generally preserved between time points and largely reproducible, suggesting that these may be more reliable. Several gene networks associated with variables related to HIV infection were found (e.g., MHC I antigen processing, TNF signaling, interferon gamma signaling, and antiviral defense); however, no significant associations were found for neurocognitive function. Furthermore, neither individual gene probes nor gene networks predicted later neurocognitive change. This study did not validate our previous findings and does not support the use of monocyte gene expression profiles as a biomarker for current or future HIV-associated neurocognitive impairment.     

Serum surrogate markers of liver fibrosis in primary biliary cirrhosis

Background

Hyaluronan, leptin, laminin and collagen IV have been used extensively for the assessment of liver fibrosis. The aim of this study was to assay these markers in the peripheral and hepatic vein blood of primary biliary cirrhosis (PBC) patients and to study their ability to discriminate early from advanced disease.

Methods

Sera from 62 PBC patients were compared to 60 controls, 44 chronic Hepatitis C, 38 hepatocellular carcinoma and 34 viral cirrhosis patients. Serum from the hepatic vein of 15 cirrhotic PBC patients and 17 patients with viral cirrhosis was also assayed.

Results

All disease groups had significantly increased levels of hyaluronan and collagen IV, compared to controls, while laminin was significantly increased only in viral cirrhosis. Hyaluronan levels were statistically different between early (54.5 ng/ml; 95%CI 27.3-426.9) and late PBC (154.5 ng/ml; 95%CI 55.3-764.4, p < 0.05). The area under the curve (AUC) for the identification of late PBC was 0.74 for hyaluronan, 0.63 for leptin, 0.59 for laminin and 0.70 for collagen IV. Hyaluronan had high sensitivity and NPV in identifying late stages of PBC (96% and 90%, respectively). Short term UDCA had no effect on these markers.

Conclusion

No single measurement can differentiate between advanced and early fibrosis in PBC. However serum hyaluronan is a promising single serum marker for longitudinal studies in PBC.     

Quiescent T cells and HIV: an unresolved relationship

The ability of HIV to infect quiescent CD4⁺ T cells has been a topic of intense debate. While early studies suggested that the virus could not infect this particular T cell subset, subsequent studies using more sensitive protocols demonstrated that these cells could inefficiently support HIV infection. Additional studies showed that the kinetics of infection in quiescent cells was delayed and multiple stages of the viral life cycle were marred by inefficiencies. Despite that, proviral DNA has been found in these cells presenting them as a potential viral reservoir. Therefore, a better understanding of the relationship between HIV and quiescent T cells may lead to further advances in the field of HIV.     

The modulation of crossmodal integration by unimodal perceptual grouping: a visuotactile apparent motion study

We adapted the crossmodal dynamic capture task to investigate the modulation of visuotactile crossmodal integration by unimodal visual perceptual grouping. The influence of finger posture on this interaction was also explored. Participants were required to judge the direction of a tactile apparent motion stream (moving either to the left or to the right) presented to their crossed or uncrossed index fingers. The participants were instructed to ignore a distracting visual apparent motion stream, comprised of either 2 or 6 lights presented concurrently with the tactile stimuli. More crossmodal dynamic capture of the direction of the tactile apparent motion stream by the visual apparent motion stream was observed in the 2-lights condition than in the 6-lights condition. This interaction was not modulated by finger posture. These results suggest that visual intramodal perceptual grouping constrains the crossmodal binding of visual and tactile apparent motion information, irrespective of finger posture.     

Temporal order judgments for audiovisual targets embedded in unimodal and bimodal distractor streams

We investigated whether the presence of unimodal or bimodal (synchronous) distractors would affect temporal order judgments (TOJs) for pairs of asynchronous audiovisual target stimuli. Participants made unspeeded TOJs regarding which of a pair of auditory and visual stimuli, presented at different stimulus onset asynchronies using the method of constant stimuli, occurred first. These asynchronous target stimuli were presented in a fixed position amongst a stream of three (auditory, visual, or audiovisual) distractors in each block of trials. The largest just noticeable differences (JNDs) were reported when the target stimuli were presented in the middle (position 3) of the distractor stream. Importantly, audiovisual distractors were shown to interfere with TOJ performance far more than unimodal (auditory or visual) distractors. The point of subjective simultaneity (PSS) was also influenced by the modality of the distractors, and by the position of the target within the distractor stream. These results confirm the existence of a specifically bimodal crowding effect, with audiovisual TOJs being impaired far more by the presence of audiovisual distractors that by unimodal auditory or visual distractors.     

Rituximab-induced nonspecific interstitial pneumonia like reaction in a patient with idiopathic thrombocytopenic purpura

Rituximab, a chimeric anti-CD20 IgG1 monoclonal antibody, is an effective treatment for haematological autoimmune diseases such as idiopathic thrombocytopenic purpura (ITP). A 72-year-old man was diagnosed with idiopathic thrombocytopenic purpura (ITP). After receiving 4 cycles of rituximab in one month complete response was achieved. However, three weeks after the last infusion he presented to the haematology department with fever, productive cough and dyspnea and severe hypoxemia. HRCT of the thorax revealed patchy areas of ground glass opacities throughout both lungs and small peripheral consolidations were seen. Transbronchial biopsy showed interstitial thickening and type II pneumocyte activation with interstitial pneumonia. Bronchoalveolar lavage showed increased eosinophils. The patient was treated with three pulses of 1 gr iv methylprednisolone and then gradually switched to 15 mg of prednisolone for 3 months. The dyspnea and tachypnea gradually improved, in addition to blood oxygenation and a follow up HRCT 3 months later showed a significant resolution of lesions.Severe lung toxicity like acute respiratory distress syndrome, cryptogenic organizing pneumonia, pneumonitis, and interstitial lung disease are very rare, with most of the knowledge coming from case reports. Rituximab-induced interstitial lung disease (R-ILD) is a rare complication. To the best of our knowledge, 23 cases of R-ILD have been reported in the literature; 22 of them were treated with R-CHOP for NHL and only one was receiving rituximab for ITP. We report the second case to develop this complication for a non-malignant disorder.     

Audiovisual synchrony perception for music, speech, and object actions

We investigated the perception of synchrony for complex audiovisual events. In Experiment 1, a series of music (guitar and piano), speech (sentences), and object action video clips were presented at a range of stimulus onset asynchronies (SOAs) using the method of constant stimuli. Participants made unspeeded temporal order judgments (TOJs) regarding which stream (auditory or visual) appeared to have been presented first. Temporal discrimination accuracy was significantly better for the object actions than for the speech video clips, and both were significantly better than for the music video clips. In order to investigate whether or not these differences in TOJ performance were driven by differences in stimulus familiarity, we conducted a second experiment using brief speech (syllables), music (guitar), and object action video clips of fixed duration together with temporally reversed (i.e., less familiar) versions of the same stimuli. The results showed no main effect of stimulus type on temporal discrimination accuracy. Interestingly, however, reversing the video clips resulted in a significant decrement in temporal discrimination accuracy as compared to the normally presented for the music and object actions clips, but not for the speech stimuli. Overall, our results suggest that cross-modal temporal discrimination performance is better for audiovisual stimuli of lower complexity as compared to stimuli having continuously varying properties (e.g., syllables versus words and/or sentences).     

Sport related plantar fasciitis. Current diagnostic and therapeutic advances

Plantar fasciitis is the most common diagnosis for pain in the inferior aspect of the heel among runners, accounting for 10% of injuries that occur in connection with running. The etiology of pain is multifactorial. The aim of the present study is to report our experience in the treatment of plantar fasciitis in athletes and compare our diagnostic strategy and treatment modalities with the current practice. MATERIAL AND METHODS: We treated 32 athletes with plantar fasciitis from 1997-2002. The diagnostic procedure included detailed history, clinical examination and imaging techniques. Conservative treatment consisted of anti-inflammatory drugs, stretching exercises, suitable training routines and special orthotic insoles, which offer a good chance of complete resolution of symptoms. Surgical fasciotomy should be reserved for use in patients in whom conservative measures have failed. RESULTS: Conservative treatment consisting of rest, anti-inflammatory medications, stretching exercises and special orthotic insoles was efficient in 26 patients (81%), while only 6 (19%) had to be treated surgically. CONCLUSION: Plantar fasciitis is a common disorder among athletes. Patient's history, clinical examination and common imaging techniques help to make the correct diagnosis. The patient should be treated conservatively at first and only in severe cases surgically.     

Optimal time for nasal packing removal after septoplasty. A comparative study

OBJECTIVE: The objective of this study was to evaluate the efficacy and subjective discomfort of one-day internal dressing compared to that of two-day in patients undergoing nasal septal surgery. STUDY DESIGN/METHODS: Prospective, randomized, clinical trial conducted on 75 patients undergoing septoplasty in a tertiary ENT clinic. Discomfort caused by nasal dressings was evaluated by means of a visual analog scale. Postoperative complications were also compared. RESULTS: Mean discomfort score for group A (nasal packing for 48 hours) was 3.5 (SD 1.15) vs. 2.7 (SD 1.52) for group B (nasal packing for 24 hours). Significant lower discomfort is reported when the nasal packing is removed the first day instead of after two or more days. No increase in complication rate was noticed. CONCLUSION: Our results point out that one-day internal nasal dressing is preferable to that of two or more days, because of less patient discomfort and increased cost-effectiveness without increasing immediate complications.